Bestrophin 1
| Bestrophin 1 | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||||||
| Symbols | BEST1 ; ARB; BEST; BMD; RP50; TU15B; VMD2 | ||||||||||||
| External IDs | OMIM: 607854 MGI: 1346332 HomoloGene: 37895 GeneCards: BEST1 Gene | ||||||||||||
| |||||||||||||
| RNA expression pattern | |||||||||||||
 | |||||||||||||
| More reference expression data | |||||||||||||
| Orthologs | |||||||||||||
| Species | Human | Mouse | |||||||||||
| Entrez | 7439 | 24115 | |||||||||||
| Ensembl | ENSG00000167995 | ENSMUSG00000037418 | |||||||||||
| UniProt | O76090 | O88870 | |||||||||||
| RefSeq (mRNA) | NM_001139443 | NM_011913 | |||||||||||
| RefSeq (protein) | NP_001132915 | NP_036043 | |||||||||||
| Location (UCSC) | Chr 11: 61.72 – 61.73 Mb | Chr 19: 9.99 – 10 Mb | |||||||||||
| PubMed search | |||||||||||||
Bestrophin-1 is a protein that in humans is encoded by the BEST1 gene.[1][2][3]
It can be associated with Vitelliform macular dystrophy.
Function
BEST1 belongs to the bestrophin family of calcium-activated anion channels, which includes BEST2, BEST3, and BEST4. Bestrophins are transmembrane (TM) proteins that share a homology region containing a high content of aromatic residues, including an invariant arg-phe-pro (RFP) motif. Bestrophins are believed to function as chloride channels that may also serve as regulators of intracellular calcium signalling.[4]
Bestrophin 1 was shown to be permeable for chloride, thiocyanate, bicarbonate, glutamate, and GABA. Bestrophin 1-mediated GABA release has recently been demonstrated to be responsible for tonic inhibition in cerebellar granule cells,[5] and has been linked to the pathology of Alzheimer's disease.[6]
Gene structure
The bestrophin genes share a conserved gene structure, with almost identical sizes of the 8 RFP-TM domain-encoding exons and highly conserved exon-intron boundaries. Each of the 4 bestrophin genes has a unique 3-prime end of variable length.[3][7][8]
BEST1 has been shown by two independent studies to be regulated by Microphthalmia-associated transcription factor.[9][10]
Interactions
Bestrophin 1 has been shown to interact with PPP2CA.[11]
Antagonists
References
- ↑ Stone EM, Nichols BE, Streb LM, Kimura AE, Sheffield VC (Jun 1993). "Genetic linkage of vitelliform macular degeneration (Best's disease) to chromosome 11q13". Nat Genet 1 (4): 246–50. doi:10.1038/ng0792-246. PMID 1302019.
- ↑ Barro Soria R, Spitzner M, Schreiber R, Kunzelmann K (Sep 2006). "Bestrophin 1 enables Ca2+ activated Cl− conductance in epithelia". J Biol Chem 284 (43): 29405–12. doi:10.1074/jbc.M605716200. PMC 2785573. PMID 17003041.
- ↑ 3.0 3.1 "Entrez Gene: BEST1 bestrophin 1".
- ↑ Hartzell HC, Qu Z, Yu K, Xiao Q, Chien LT (April 2008). "Molecular physiology of bestrophins: multifunctional membrane proteins linked to best disease and other retinopathies". Physiol. Rev. 88 (2): 639–72. doi:10.1152/physrev.00022.2007. PMID 18391176.
- ↑ Lee S, Yoon BE, Berglund K, Oh SJ, Park H, Shin HS, Augustine GJ, Lee CJ (November 2010). "Channel-mediated tonic GABA release from glia". Science 330 (6005): 790–6. doi:10.1126/science.1184334. PMID 20929730.
- ↑ Jo, Seonmi (2014). "GABA from reactive astrocytes impairs memory in mouse models of Alzheimer's disease". Nature Medicine 20 (8): 886–896. doi:10.1038/nm.3639.
- ↑ Stöhr H, Marquardt A, Nanda I, Schmid M, Weber BH (April 2002). "Three novel human VMD2-like genes are members of the evolutionary highly conserved RFP-TM family". Eur. J. Hum. Genet. 10 (4): 281–4. doi:10.1038/sj.ejhg.5200796. PMID 12032738.
- ↑ Tsunenari T, Sun H, Williams J, Cahill H, Smallwood P, Yau KW, Nathans J (October 2003). "Structure-function analysis of the bestrophin family of anion channels". J. Biol. Chem. 278 (42): 41114–25. doi:10.1074/jbc.M306150200. PMC 2885917. PMID 12907679.
- ↑ Esumi N, Kachi S, Campochiaro PA, Zack DJ (2007). "VMD2 promoter requires two proximal E-box sites for its activity in vivo and is regulated by the MITF-TFE family". J. Biol. Chem. 282 (3): 1838–50. doi:10.1074/jbc.M609517200. PMID 17085443.
- ↑ Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
- ↑ Marmorstein LY, McLaughlin PJ, Stanton JB, Yan L, Crabb JW, Marmorstein AD (2002). "Bestrophin interacts physically and functionally with protein phosphatase 2A". J. Biol. Chem. 277 (34): 30591–7. doi:10.1074/jbc.M204269200. PMID 12058047.
- ↑ Rao PR. Identification of novel selective antagonists for Bestrophin-1 protein by homology modeling and molecular docking. International Journal of Pharmacy and Pharmaceutical Sciences 2012; 4(S4):195-200.
Further reading
- White K, Marquardt A, Weber BH (2000). "VMD2 mutations in vitelliform macular dystrophy (Best disease) and other maculopathies". Hum. Mutat. 15 (4): 301–8. doi:10.1002/(SICI)1098-1004(200004)15:4<301::AID-HUMU1>3.0.CO;2-N. PMID 10737974.
- Nordström S, Barkman Y (1977). "Hereditary maculardegeneration (HMD) in 246 cases traced to one gene-source in central Sweden". Hereditas 84 (2): 163–76. doi:10.1111/j.1601-5223.1977.tb01394.x. PMID 838599.
- Forsman K, Graff C, Nordström S et al. (1992). "The gene for Best's macular dystrophy is located at 11q13 in a Swedish family". Clin. Genet. 42 (3): 156–9. doi:10.1111/j.1399-0004.1992.tb03229.x. PMID 1395087.
- Stöhr H, Marquardt A, Rivera A et al. (1998). "A gene map of the Best's vitelliform macular dystrophy region in chromosome 11q12-q13.1". Genome Res. 8 (1): 48–56. doi:10.1101/gr.8.1.48. PMC 310689. PMID 9445487.
- Petrukhin K, Koisti MJ, Bakall B et al. (1998). "Identification of the gene responsible for Best macular dystrophy". Nat. Genet. 19 (3): 241–7. doi:10.1038/915. PMID 9662395.
- Pennisi E (1998). "New gene found for inherited macular degeneration". Science 281 (5373): 31. doi:10.1126/science.281.5373.31. PMID 9679014.
- Marquardt A, Stöhr H, Passmore LA et al. (1998). "Mutations in a novel gene, VMD2, encoding a protein of unknown properties cause juvenile-onset vitelliform macular dystrophy (Best's disease)". Hum. Mol. Genet. 7 (9): 1517–25. doi:10.1093/hmg/7.9.1517. PMID 9700209.
- Caldwell GM, Kakuk LE, Griesinger IB et al. (1999). "Bestrophin gene mutations in patients with Best vitelliform macular dystrophy". Genomics 58 (1): 98–101. doi:10.1006/geno.1999.5808. PMID 10331951.
- Bakall B, Marknell T, Ingvast S et al. (1999). "The mutation spectrum of the bestrophin protein--functional implications". Hum. Genet. 104 (5): 383–9. doi:10.1007/s004390050972. PMID 10394929.
- Allikmets R, Seddon JM, Bernstein PS et al. (1999). "Evaluation of the Best disease gene in patients with age-related macular degeneration and other maculopathies". Hum. Genet. 104 (6): 449–53. doi:10.1007/s004390050986. PMID 10453731.
- Palomba G, Rozzo C, Angius A et al. (2000). "A novel spontaneous missense mutation in VMD2 gene is a cause of a best macular dystrophy sporadic case". Am. J. Ophthalmol. 129 (2): 260–2. doi:10.1016/S0002-9394(99)00327-X. PMID 10682987.
- Lotery AJ, Namperumalsamy P, Jacobson SG et al. (2000). "Mutation analysis of 3 genes in patients with Leber congenital amaurosis". Arch. Ophthalmol. 118 (4): 538–43. doi:10.1001/archopht.118.4.538. PMID 10766140.
- Lotery AJ, Munier FL, Fishman GA et al. (2000). "Allelic variation in the VMD2 gene in best disease and age-related macular degeneration". Invest. Ophthalmol. Vis. Sci. 41 (6): 1291–6. PMID 10798642.
- Krämer F, White K, Pauleikhoff D et al. (2000). "Mutations in the VMD2 gene are associated with juvenile-onset vitelliform macular dystrophy (Best disease) and adult vitelliform macular dystrophy but not age-related macular degeneration". Eur. J. Hum. Genet. 8 (4): 286–92. doi:10.1038/sj.ejhg.5200447. PMID 10854112.
- Marmorstein AD, Marmorstein LY, Rayborn M et al. (2001). "Bestrophin, the product of the Best vitelliform macular dystrophy gene (VMD2), localizes to the basolateral plasma membrane of the retinal pigment epithelium". Proc. Natl. Acad. Sci. U.S.A. 97 (23): 12758–63. doi:10.1073/pnas.220402097. PMC 18837. PMID 11050159.
- Marchant D, Gogat K, Boutboul S et al. (2001). "Identification of novel VMD2 gene mutations in patients with best vitelliform macular dystrophy". Hum. Mutat. 17 (3): 235. doi:10.1002/humu.9. PMID 11241846.
- Eksandh L, Bakall B, Bauer B et al. (2001). "Best's vitelliform macular dystrophy caused by a new mutation (Val89Ala) in the VMD2 gene". Ophthalmic Genet. 22 (2): 107–15. doi:10.1076/opge.22.2.107.2226. PMID 11449320.
- Sun H, Tsunenari T, Yau KW, Nathans J (2002). "The vitelliform macular dystrophy protein defines a new family of chloride channels". Proc. Natl. Acad. Sci. U.S.A. 99 (6): 4008–13. doi:10.1073/pnas.052692999. PMC 122639. PMID 11904445.
- Xiao Q, Yu K, Cui YY, Hartzell HC (2009). "Dysregulation of human bestrophin-1 by ceramide-induced dephosphorylation". J Physiol. 587 (18): 4379–91. doi:10.1113/jphysiol.2009.176800. PMC 2766645. PMID 19635817.
- Xiao Q, Prussia A, Yu K, Cui YY, Hartzell HC (2008). "Regulation of bestrophin Cl channels by calcium: role of the C terminus". J Gen Physiol. 132 (6): 681–92. doi:10.1085/jgp.200810056. PMC 2585866. PMID 19029375.
External links
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||